Liver X receptor β and thyroid hormone receptor α in brain cortical layering

Xin Jie Tan, Xiao Tang Fan, Hyun Jin Kim, Ryan Butler, Paul Webb, Margaret Warner, Jan Åke Gustafsson

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

In the past year, two members of the nuclear receptor family, liver X receptor β (LXRβ) and thyroid hormone receptor α (TRα), have been found to be essential for correct migration of neurons in the developing cortex in mouse embryos. TRα and LXRβ bind to identical response elements on DNA and sometimes regulate the same genes. The reason for the migration defect in the LXRβ-/- mouse and the possibility that TRα may be involved are the subjects of the present study. At E15.5, expression of reelin and VLDLR was similar but expression of apolipoprotein E receptor 2 (ApoER2) (the reelin receptor) was much lower in LXRβ -/- than in WT mice. Knockout of ApoER2 is known to lead to abnormal cortical lamination. Surprisingly, by postnatal day 14 (P14), no morphological abnormalities were detectable in the cortex of LXRβ-/- mice and ApoER2 expression was much stronger than in WT controls. Thus, a postnatal mechanism leads to increase in ApoER2 expression by P14. TRα also regulates ApoER2. In both WT and LXRβ-/- mice, expression of TRα was high at postnatal day 2. By P14 it was reduced to low levels in WT mice but was still abundantly expressed in the cortex of LXRβ -/- mice. Based on the present data we hypothesize that reduction in the level of ApoER2 is the reason for the retarded migration of later-born neurons in LXRβ-/- mice but that as thyroid hormone (TH) increases after birth the neurons do find their correct place in the cortex.

Original languageEnglish (US)
Pages (from-to)12305-12310
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number27
DOIs
StatePublished - Jul 6 2010

Keywords

  • Apolipoprotein E receptor 2
  • Cerebral cortex
  • Development
  • Embryo

ASJC Scopus subject areas

  • General

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